Enhancing care quality and accessibility through digital technology-supported decentralisation of hypertension and diabetes management: a proof-of-concept study in rural Bangladesh

Objective The critical shortage of healthcare workers, particularly in rural areas, is a major barrier to quality care for non-communicable diseases (NCD) in low-income and middle-income countries. In this proof-of-concept study, we aimed to test a decentralised model for integrated diabetes and hypertension management in rural Bangladesh to improve accessibility and quality of care. Design and setting The study is a single-cohort proof-of-concept study. The key interventions comprised shifting screening, routine monitoring and dispensing of medication refills from a doctor-managed subdistrict NCD clinic to non-physician health worker-managed village-level community clinics; a digital care coordination platform was developed for electronic health records, point-of-care support, referral and routine patient follow-up. The study was conducted in the Parbatipur subdistrict, Rangpur Division, Bangladesh. Participants A total of 624 participants were enrolled in the study (mean (SD) age, 59.5 (12.0); 65.1% female). Outcomes Changes in blood pressure and blood glucose control, patient retention and patient-visit volume at the NCD clinic and community clinics. Results The proportion of patients with uncontrolled blood pressure reduced from 60% at baseline to 26% at the third month of follow-up, a 56% (incidence rate ratio 0.44; 95% CI 0.33 to 0.57) reduction after adjustment for covariates. The proportion of patients with uncontrolled blood glucose decreased from 74% to 43% at the third month of follow-up. Attrition rates immediately after baseline and during the entire study period were 29.1% and 36.2%, respectively. Conclusion The proof-of-concept study highlights the potential for involving lower-level primary care facilities and non-physician health workers to rapidly expand much-needed services to patients with hypertension and diabetes in Bangladesh and in similar global settings. Further investigations are needed to evaluate the effectiveness of decentralised hypertension and diabetes care.

The design of the study is a description of a single cohort and should be clarified in the methods section.Statistical analysis Page 16 -Row 29: The authors mention that given the nature of continuous enrolment, patients recruited earlier had a lengthier follow-up compared with those entered the study later.This needs to be discussed further and clarify if the GEE Poisson model used included the exposure time of each individual in order to correctly estimate the IRR.This does not generate a bias if the follow-up time of each one was included in the Poisson analysis.

Results
Page 18 -Row 53: The authors report a 56% reduction in the probability of having uncontrolled blood pressure after adjustment for covariates (from 60% at baseline to 26%) at the third month of follow-up, but this group returns to the baseline proportion of poor control at 6 months.Please add a brief comment about this finding.Page 19 -Row 6: The authors mention that the attrition rates immediately after baseline and during the entire study period were 29.1% and 36.2%respectively, which are quite high for a short term cohort.Please add a brief comment about the potential bias induced by this proportion of patients lost to follow-up.Response.While we agree that the term "proof-of-concept" is perhaps not used as widely as "feasibility" or "pilot",6 we believe that 'proof-of-concept' is more appropriate to describe our trial as our study specially aims to investigate a novel intervention.Accordingly, we have added a few details to clarify our study as a proof-of-concept, small-scale investigation: "In the present proof-of-concept study, we aimed to 1) generate preliminary data on the effectiveness of a novel digital technology supported decentralization of primary care diabetes and hypertension management in a rural subdistrict in Northern Bangladesh, and 2) to understand its potential future implications for the patient care pathway, the patient load in primary care facilities at a subdistrict and village level, and patient retention."Methods Study design Comment 2.5 Page 11 -Row 6: The design of the study is a description of a single cohort and should be clarified in the methods section.
Response.We have made the recommended change: "The study is a single cohort proof-of-concept study.Decentralized hypertension and diabetes care comprised screening, routine monitoring, and dispensing of …" Statistical analysis Comment 2.6 Page 16 -Row 29: The authors mention that given the nature of continuous enrolment; patients recruited earlier had a lengthier follow-up compared with those entered the study later.This needs to be discussed further and clarify if the GEE Poisson model used included the exposure time of each individual in order to correctly estimate the IRR.This does not generate a bias if the follow-up time of each one was included in the Poisson analysis.
Response.Exposure time was included as the key independent variable to quantify the change in blood pressure and blood glucose control using binary dummy variables for each follow-up time point relative to the baseline.We added this information in the statistical analysis section.
"Changes in proportion of patients with an uncontrolled condition were analysed with generalized estimating equation (GEE) Poisson regression with robust variance.Follow-up visit was included as binary indicators in the regression model to capture the change in blood pressure and blood glucose control relative to the baseline."

Results
Comment 2.7 Page 18 -Row 53: The authors report a 56% reduction in the probability of having uncontrolled blood pressure after adjustment for covariates (from 60% at baseline to 26%) at the third month of follow-up, but this group returns to the baseline proportion of poor control at 6 months.Please add a brief comment about this finding.
Response.The proportion of patients with uncontrolled blood pressure at 6 month was 39% as compared with 60% at baseline (Figure 2).The reviewer is right that although there was a 36% difference, it was not statistically significant (IRR 0.64; 95% CI 0.32, 1.25).We have added a sentence to clarify this finding.
"Amongst the 549 patients with hypertension, the ageand sex-adjusted proportion of people with uncontrolled blood pressure decreased from 60% (95% CI, 56%, 64%) at baseline to 26% (95% CI, 19%, 33%) at the third month of follow-up (Figure 2), a 56% (IRR 0.44; 95% CI, 0.33, 0.57) reduction in the probability of having uncontrolled blood pressure after adjustment for covariates (Table 2).The proportion of people with uncontrolled blood pressure rebounded to 39% (95% CI, 12%, 65%) at the fifth month of follow-up, and the difference was no longer statistically significant compared with the proportion at baseline (IRR 0.64; 95% CI, 0.32, 1.25), although the number of observations at the fifth visit (n=20) was notably smaller relative to baseline (n=549)."Comment 2.8 Page 19 -Row 6: The authors mention that the attrition rates immediately after baseline and during the entire study period were 29.1% and 36.2%respectively, which are quite high for a short-term cohort.Please add a brief comment about the potential bias induced by this proportion of patients lost to follow-up.
Response.It is widely recognized that patient retention is a tremendous challenge in hypertension and diabetes care largely due to the fact that these conditions are often asymptomatic and not immediately life-threatening.The present study was designed to test the modified care pathways and patient retention in a real-world setting rather than a highly controlled context such as with an efficacy trial.As elaborated in the discussion, the observed rates of dropping out of the study compare favorably with previous implementation studies.7,8To evaluate the potential biases introduced by sample attrition, we conducted sensitivity analyses (results shown in Supplementary Table 3), estimating the key results with inverse probability weighting using the predicted probability of dropping out from the study from a conditional logit model with the same set of covariates, as well as restricting the analyses to patients with 3 or more follow-up visits, and the results appeared to be robust.
While the robustness of our results to potential sample attrition bias was examined, we recognize that the discussion section could be strengthened with a brief discussion on the factors associated with attrition and the decreasing attrition incidence.A paragraph has now been added in the discussion section for this purpose.
"Our findings showed several factors were associated with loss to follow-up, including being newly diagnosed, having a controlled condition at enrolment, and/or being diagnosed with hypertension only.In addition, the results showed a particularly high attrition rate immediately after enrolment, consistent with previous studies.7,8Attrition incidence appeared to decrease with longer follow-up despite higher cumulative attrition rates over time, likely due to the depletion of individuals with high propensity of dropping out.These observations may have important implications for routine healthcare delivery to improve patient retention.Additional efforts may be needed to emphasize the need for regular follow-up to newly diagnosed patients, those with controlled status at enrolment, and those detected with hypertension only, especially at enrolment." Introduction Page 9 -Row 5: Describing it as a proof of concept is not clear for the average reader.It would be important to briefly clarify what this definition represents, to facilitate understanding by readers.Kendig CE.What is Proof of Concept Research and how does it Generate Epistemic and Ethical Categories for Future Scientific Practice?Sci Eng Ethics.2016 Jun;22(3):735-53.doi: 10.1007/s11948-015-9654-0. Epub 2015 May 26.PMID: 26009258 What is Proof of Concept Research and how does it Generate Epistemic and Ethical Categories for Future Scientific Practice?Sci Eng Ethics.2016 Jun;22(3):735-53.doi: 10.1007/s11948-015-9654-0. Epub 2015 May 26.PMID: 26009258